The objectives in this project are to determine whether tyrosine kinase substrates of the EGF receptor, which have been identified in cell cultures only, are, in fact, substrates in respiratory tissue. Thus, the proposed work will demonstrate whether phospholipase Cgamma, GAP, and PI-3 kinase are activated by tyrosine phosphorylation in EGF-treated respiratory tissue. It is anticipated that these molecules are receptor proximal in the mitogenic signaling pathway and lead to early responses, such as the induction of early genes and/or membrane changes. Other aspects of this project include the potential identification of new tyrosine kinases and tyrosine kinase substrates in respiratory tissue. One would anticipate that any normal function or pathology of these tissues, including cell renewal, wound healing, dysplasia, would involve the activation of these molecules.